Researchers at Oregon State University have discovered a groundbreaking way to make breast cancer cells self-destruct.
They found new compounds that change a protein known for protecting cancer cells into one that kills them.
This discovery opens the door to new treatments for breast cancer and other cancers that use this protein, called Bcl-2, to resist drugs and treatments.
Dr. Siva Kolluri, a professor in the College of Agricultural Sciences, explained the significance of this discovery.
“The ultimate goal in cancer research is to find a way to target cancer cells without harming normal cells,” he said. “Cancer cells hijack normal pathways that control cell growth and death.”
Normally, cells go through a programmed death process called apoptosis, which is like a natural recycling system for cells.
However, cancer cells find ways to block this process, allowing them to grow uncontrollably and spread to other parts of the body.
The Bcl-2 protein is known for its role in preventing cell death. Some cancer cells produce high levels of Bcl-2, making it a target for drug researchers.
While blocking Bcl-2 has been effective in treating some blood cancers, it hasn’t worked well for solid tumors like breast cancer.
“Cancer cells are very clever,” Kolluri said. “They find ways to survive treatments. It’s like stopping a car only to have it start moving again. But with our discovery, it’s like taking the wheels off the car completely.”
Kolluri and his colleague, Professor Christiane Löhr, focused their research on triple-negative breast cancer, one of the most aggressive forms of the disease. Triple-negative breast cancer lacks three specific receptors found in other types of breast cancer, making it harder to treat. It makes up about 20% of all breast cancer cases and includes some of the worst prognoses.
In their studies, the researchers tested new compounds on triple-negative breast cancer cells in lab cultures and mouse models.
Their first study, published in Cancer Research Communications, showed how they found and tested a compound that changes the shape of the Bcl-2 protein. This change exposes Bcl-2’s “killer conformation,” leading to cancer cell death.
Their second study, published in ACS Pharmacology & Translational Science, demonstrated that another compound could kill breast cancer cells in lab cultures and prevent breast cancer from spreading to the lungs in mice. The lungs are a common site for breast cancer metastasis.
“This is very promising because many metastatic cancers have high Bcl-2 levels,” Löhr said. “This increased Bcl-2 expression is also common in cancer that has become resistant to treatments.”
The researchers emphasize that their findings are the result of years of detailed research. They discovered that a protein normally involved in regulating genes in the nucleus also kills cells by moving to the mitochondria, where it interacts with Bcl-2 and changes its function.
“A breakthrough like this takes many years of work,” Löhr said. “We’ve shown proof of concept and the potential to target cancers that resist other treatments while leaving normal cells unharmed.”
The next steps for the researchers include finding partners to advance this research towards clinical trials in humans and further testing in preclinical models. Their work also has potential applications beyond human medicine, such as treating lymphoma in dogs.
Other contributors to this research include Prasad Kopparapu, Martin Pearce, Shanthakumar Tyavanagimatt from OSU, and Harikrishna Nakshatri from Indiana University School of Medicine.
This discovery represents a significant step forward in the fight against cancer, offering hope for new, more effective treatments in the future.
